Perfluoroalkanesulfonamides N-substituted by heterocyclic groups

ABSTRACT

N-Substituted perfluoroalkanesulfonamides in which the sulfonamide nitrogen substituent is a heteroatom-containing group selected from pyridinyl, quinolinyl, pyrazolyl, thiazolyl, quinoxalinylphenyl, imidazo (1,2a) pyridinylphenyl, imidazo (1,2a) pyrimidylphenyl and benzoxazolyl which can be unsubstituted or which can carry certain substituents. Also included are salts of these compounds, compositions containing the compounds of the present invention and processes for their preparation and use. The compounds are active as herbicides and plant growth modifiers.

United States Patent Harrington et al. 1 Dec. 2, 1975 1 1 PERFLUOROALKANESULFONAMIDES 3,268,538 8/1966 Billman 260/283 SA N SUBSTITUTED BY HETEROCYCLIC 3,321,445 5/1967 Luzerte... 260/3l.2 R GROUPS 3,337,555 8/1967 Billman .1 260/283 SA [75] Inventors: Joseph Kenneth Harrington, Edina; OTHER PUBLICATIONS Donald m, North Oaks; Robertson et al., CA 71, 495715 (1969). Arthur Mendel Vadnais Heights 2, 3 Jerry E. Robertson, North Oaks, all Hamngton at a] CA 7 12118 g (970) of Minn. I Primary ExaminerDonald G. Daus [73] Assigneez Minnesota lvlinlng and Assistant Examiner-Mark L. Berch Mfmufactul'mg p y, Paul, Attorney, Agent, or FirmAlexander, Sell, Steldt & DeLaHunt [22] Filed: Jan. 28, 1974 1211 Appl. No.: 437,499 [57] ABSTRACT Related Us Application Data N-Substituted perfluoroalkanesulfonamides in which 60 D f5 '142 8 M H 1971 P N the sulfonamide nitrogen substituent is a heteroatom- 3 El 6 1 2 8; a n d a continuzit ion ii-part of 5s N8 containing grqup selected.from .pyridinyl qui.no.linyl 837,932, .lune 30, 1969, Pat. No. 3,637,729, which 18' pyrazolyl Flulnoxalmylphenyl. a continuation-in-part of Ser. No. 588,338, Oct. 21, [L23] Pyndmylphenyl "mdazo [12a] pynmldylphe' 1966, aband0ned nyl and benzoxazolyl which can be unsubstituted or which can carry certain substituents. [52] U.S. Cl 260/270 D; 260/283 SA; 424/258 Also included are salts of 'these compounds, [51] Int. Cl. C07D 215/40 compositions containing the compounds of the present Field of Search 2 3 270 D invention and processes for their preparation and use. The compounds are active as herbicides and plant [5 6] References Cited growth modifiers.

UNITED STATES PATENTS 1/1956 Brice 260/247.1 R

5 Claims, No Drawings PERFLUOROALKANESULFONAMIDES N-SUBSTITUTED BY HETEROCYCLIC GROUPS This is a division of application Ser, No. 142,381, filed May 11, 1971, now US. Pat. No. 3,801,588, and a continuation-in-part of application Ser. No. 837,932 now US. Pat. No. 3,637,729 filed June 30, 1969, which is, in turn a continuation-in-part of application Ser. No. 588,338 filed Oct. 21, 1966, now abandoned.

The invention relates to perfluoroalkanesulfonamides, N-substituted by heterocyclic ring-containing groups, said compounds having activity as herbicides and plant growth modifiers, and particularly as preemergence herbicides Perfluoroalkanesulfonamides have been disclosed broadly heretofore (see, for example, US. Pat. Nos. 2,732,398 and 3,321,445) but there has been no indication of any herbicidal activity of such compounds.

In the N-substituted perfluoroalkanesulfonamides of the present invention, the sulfonamide nitrogen substituent is a heterocyclic ring-containing group selected from pyridinyl, quinolinyl, pyrazolyl, thiazolyl, quinoxalinylphenyl, imidazo [1,2a] pyridinylphenyl, imidazo [1,2211 pyrimidylphenyl and benzoxazolyl, said groups being unsubstituted or substituted. The invention also includes salts of the compounds, processes for their preparation, compositions containing them and methods for their use as herbicides, and plant growth modifiers.

It is an object of the invention to provide compounds which modify the growth of plants, i.e. compounds which prevent, alter, destroy or otherwise affect the growth of plants.

It is a further object of the invention to provide a method for controlling unwanted plants.

It is another object of the invention to provide herbicidal compositions containing one or more perfluoroalkanesulfonamides as active ingredients therein.

Still other objects of the invention will be made apparent by the following specification.

DETAILED DESCRIPTION According to the present invention, there is provided a class of compounds consisting of perfluoroalkanesulfonamides having the general formula:

and metal, ammonium and organic amine salts thereof wherein R, is a p'erfluoroalk'yl group containing one to four carbon atoms, Het is selected from pyridinyl, quinolinyl. pyrazolyl, thiazolyl, quinoxalinylphenyl, imidazo [1,2a] pyridinylphenyl, imidazo [1,2a] pyrimidylphenyl and bent-:oxazolyl, Y is lower alkyl, halogen, cyano, lower alkoxy, nitro, amino or lower alkanolylamido and n is (L2 when Het is thia'zolyl and is otherwise O3. When n is aero, the Het group in the compound is not substituted by any Y groups, i.e. hydrogen appears in place of the Y groups. The compounds of the invention in which n is 0 or, in which n is 1 form preferred classes of compounds of the invention."

In the metal, ammonium and organic amine salts, the sulfonamide hydrogen of the formula is replaced by a suitable cation. 1 i

"i he salts of the invention are prepared by treatingthe acid form (shown in the foregoing Formula I) with a stoichiornetrically equivalent amount of an appropri- 2 ate base under mild conditions. Among the metal salts of the invention are alkali metal (e.g. lithium, sodium and potassium), alkaline earth metal (e.g. barium, calcium and magnesium) and heavy metal (e.g. Zinc and iron) salts-as well as other metal salts such as aluminum. Appropriate bases for use in preparing the metal salts include metal oxides, hydroxides. carbonates, bicarbonates and alkoxides. Some salts are also prepared by transmetallation reactions. The organic amine salts include the salts of alkylamines and aromatic amines, primary, secondary or tertiary. These and the ammonium salts can be prepared by reacting the acid form with the appropriate organic base or ammonium hydroxide. The salts of the invention are frequently formed by reacting the precursors in aqueous solution.

This solution can be evaporated to obtain the salt of the compound usually as a dry powder. In some cases, it

may be more convenient to use a non-aqueous solvent Preferably, R, in the compounds of the invention is trifluoromethyl. Price is an important consideration in herbicides and such compounds offer more-economical utilization of fluorine together with high activity. The group Het-Yn in the compounds usually and preferably contains not more than about 16 carbon atoms. The various Ys in a compound can be the same or different. Preferably, no Y group contains more than four carbon atoms. Particularly preferred groups of compounds of the invention are those in which Het is a thiazole ring. 1

In order to control unwanted plants, the compounds of the invention can be used alone as herbicides, for ex ample, as dusts or granules of the compounds, or preferably they may be applied in formulations containing the active ingredients in a horticulturally acceptable extending medium. The formulations are comprised of one or more active ingredients and one or more herbicidal diluents, adjuvants and/or carriers. Specific formulations are useful to facilitate the application of the compounds and to achieve specific biological objectives such as controlling the availability of the herbicide, improving adherence to plants, and the like, as is well known to thoseskilled in the art.

A presently especially preferred herbicidal com-' pound of this invention is 2-trifluoromethanesulfonamidothiazole.

The compounds of this invention are broadly active as herbicides. However, many of the compounds of this invention also show various types of plant growth modifying activity. Plant growth modification as defined herein consists of all deviations from natural development, for example, defoliation, stimulation, stunting, retardation, desiccation, tillering, dwarfing, regulation and the like. This plant growth modifying activity is generally observed as the compounds of the invention begin to interfere with certainprocesses within the plant. If these processes are essential, the plant will die if treated with a sufficient dose of the compound. However, the type of growth modifying activity observed varies among types of plants. It has been found that with certain compounds of the invention, herbicidal activity can be separated from certain other plant growth modifying activities by controlling the rate of application.

Broadly speaking, the compounds of this invention are readily prepared by one or all of the following methods, each of which is illustrated by an equation.

METHOD A essary, and an excess of the primary amine may also serve as acid acceptor. Among the suitable solvents are 1,2-dimethoxyethane, benzene, chloroform, dichloromethane, dimethylacetamide, dimethylformamide and the like. Alternatively, an excess of the primary amine or the acid acceptor may serve as a solvent, or the reaction may be carried out in the absence of solvent. Generally, an equimolar quantity of the appropriate perfluoroalkanesulfonic anhydride or halide is added to the solution. The addition is advantageously carried out at 1 5 C. to 100 C., and for some reactants higher or lower temperatures may be preferable. In cases where the amine is of lower reactivity, it is advantageous to allow the reaction mixture to remain at reflux temperature for a few hours following addition.

The reaction of Method A may also be carried out in a high pressure reactor. This technique is particularly preferred when perfluoroalkanesulfonyl fluorides are used as reactants. These reactions are usually carried out at temperature ranges of 0 to 150 C., but these temperature ranges may be raised or lowered, depending upon the reactants used. Such reactions are most frequently carried out without solvent, or with dimethylformamide or excess triethylamine as solvent, but other advantageous variations are possible.

It will be appreciated that the scope of this invention encompasses starting materials of a wide range of physical and chemical properties, and the synthetic methods A, B and C discussed herein are described in general and preferred language. However, a great variation in the use of these synthetic techniques is possible, and this invention is broadly inclusive of such variations.

After completion of the reaction, the product is isolated by conventional methods. For example, the reaction mixture can be extracted with excess aqueous sodium hydroxide. The aqueous extract is then washed with organic solvents and treated with charcoal to remove impurities. Subsequent acidification of the aqueous extract with mineral acid then affords the product as an oil or solid which is distilled, sublimed, chromatographed or recrystallized as required to give pure product. When water-soluble solvents are used, the reaction mixture can be poured directly into aqueous mineral 4 acids. The product is then isolated by conventional extraction techniques and purified as above.

METHOD B where M is an alkali metal and O, R Het, Y and n are as defined above.

An alkali metal salt of the appropriate amine is prepared by any of several conventional methods such as by reaction with sodium naphthalene, a metal hydride such as sodium hydride, alkoxides such as potassium t-butoxide in protic or aprotic solvents, or by reaction with an alkali metal such as sodium or potassium directly in an appropriate solvent.

The resulting salt isthen treated with a perfluoroalkanesulfonyl alkylating agent such as trifluoromethanesulfonyl fluoride or chloride or trifluoromethanesulfonic anhydride, either at atmospheric pressure in open apparatus or under pressure in a pressure vessel. The reaction takes place at 0 to C., depending on the reactivity of the amine and the sulfonyl halide. On completion of the reaction, the product is obtained by conventional work-up techniques as described in Method A.

METHOD C R SO NHZ X-Het-Y,, R,SO NH-Het-Y,, ZX

(lll) R,, Y, n and Het are as defined above, X is halogen and Z is an alkaline earth or alkali metal. The perfluoroalkanesulfonamide salt and an appropriate halide of Formula III are reacted, generally in a suitable solvent (such as dimethylsulfoxide, dimethylformamide, 1,2- dimethoxyethane, dimethylacetamide and the like). Heating or cooling, usually the former, may be advantageous to obtain a desirable rate of reaction.

After the completion of the reaction, the product is isolated by conventional methods. For example, when the reaction mixture is diluted with water the product may precipitate. Alternatively, the product may be extracted from the reaction mixture after dilution with water. Other recovery techniques are well known to those skilled in the art.

The reaction of Method C may also be carried in a high pressure reactor.

Method C is usually most valuable when the halide is activated by suitable electron-withdrawing groups on the ring, as is well known to the art. Suitable halides for use in Method C are well known to the art, as are salts of perfluoroalkanesulfonamides.

Suitable perfluorocarbonsulfonyl anhydrides and halides (e.g. chlorides and fluorides) for use in these procedures are known to the art (thus see US Pat. No. 2,732,398). Similarly, the amines used in producing the compounds of this invention are described in the general chemical literature or may be prepared by methods known to those skilled in the art.

Methods A, B and C are generally applicable (preferably Method A) to the preparation of compounds of the invention. However, it is sometimes preferable, in order to increase yields and minimize purification problems, to utilize compounds of the invention in conventional, known procedures to prepare other compounds of the invention. For example, compounds wherein Y is nitro may be reduced by conventional methods to obtain compounds wherein Y is amino.

The following examples are given for the purpose of further illustrating the procedures of the present invention, but are not intended, in any way, to be limiting on the scope thereof. Thus while the examples relate to perfluoromethanesulfonamides. other perfluorocarbon groups can be substituted in place thereof. Also, although the examples relate for the most part to compounds in the acid form (that is having a hydrogen atom bonded to the amide nitrogen), it is understood that the corresponding salts of the invention are also easily prepared and are likewise contemplated. Such salts, which have a cation bonded to the sulfonamide nitrogen, are also useful as herbicides, and in some cases as plant growth modifiers.

EXAMPLE 1 This preparation was carried out using Method A as follows:

2-Amino-4-methylpyridine (54.1 g., 0.50 mole), triethylamine (250 ml.) and trifluoromethanesulfonyl fluoride (76.1 g., 0.50 mole) were heated at 90 C. for about one day. To this mixture was added excess sodium hydroxide percent) and the mixture was steam distilled to remove triethylamine. The residue was treated with decolorizing charcoal, filtered, then acidified with concentrated hydrochloric acid. The solid product was collected by filtration, recrystallized from isopropanol then sublimed to give N-[2-(4- methylpyridyl)]trifluormethanesulfonamide, m.p. 220.5-222C.

Analysis: 71C /H 71N Calculated for c,H,F.,N,o.,s; 35.0 2.9 l 1.7 Found: 35.0 2.9 11.9

The following table lists compounds of the invention prepared according to Method A as described above.

-continued Example Number Compound M.P. (in C.)

methancsulfonamidc l8 N-l3-(2-chloropyridyl)]trifluoro- 1185-1205 methancsulfonamidc 19 N-[5-( Z-n-butoxypyridyl jtrifluoro- 84.5-86.5

methancsulfonamidc 21) N-l2-(4.6-dimethylpyridyl)ltrifluoro- 127-128 mcthancsulfonamidc 21 2-( 4-trifluoromcth \'lsulfonamido- 250 phcnyl) imidazol1.2alpyrimidinc EXAMPLE 22 Analysis: /iC /(H Calculated for C H F N O S: 36.1 19 Found: 36.2 1.9

EXAMPLE 23 N-[2-( 5 -nitropyridyl) ]trifluoromethanesulfonamide (20 g., 0.074 mole) in ethanol (250 ml.) was reduced over palladium on charcoal with hydrogen gas. The catalyst was removed by filtration and 'the ethanol evaporated in vacuo to give N-[2-(5 aminopyridyl)]trifluoromethanesulfonamide. f

N-[2-( S-aminopyridyl ]trifluoromethanesulfonamide (12 g., 0.05 mole), acetyl chloride (3.92 g., 0.050 mole) and triethylamine (5.1 g., 0.05 mole) in benzene ml.) were stirred overnight. The volatile portions were removed in vacuo and the residue recrystallized from a water-ethanol mixture to give N-[2-(5- acetamidopyridyl)]trifluoromethanesulfonamide, m.p. 266267.5 C.

Analysis: 71C 7(H 7(N Calculated for CMHNFQNQOQS: 33.9 2.9 14.8

Found 34.0 2.8 15.

EXAMPLE 24 N-( 2-thiazolyl )trifluo romethanesulfonamide (25.6

g., 0.10 mole) was mixed with percent ethanol (300 ml.) and water (50 ml.) and bromine (32.0 g., 0.2 mole) was added drop-wise with stirring. The reaction was stirred at room temperature for 2 hours, then warmed to 50 C. for 30 minutes. The reaction mixture was added to ice water (1.5 l.) and the product collected by filtration. Recrystallization from benzene gave N-[ 2-( S-bromothiazolyl ]trifluoromethanesulfonamide, m.p. 195.3198 C.

Analysis: C 71H 92X Calculated for C H. .Br- .F;,N O S. 15.4 0.6 9.0 Found: 15.6 0.7 0.1

EXAMPLE Analysis: 71C l'l "/(N Calculated for C H C1F; N- O- S. 18.0 0.8 10.5 Found: 182 0.7 10.3

Example 26 I Representative salts of the invention which have been prepared are: I 1

Sodium N-(2-pyridyl)trifluoromethanesulfonamide (partially purified sample decomposes l50-165 C.) Zinc N-( 8-quinolinyl)trifluoromethanesulfonamide m.p. greater than 300 C. Analysis for C- ,l-l F N O S Zn Calculated: C, 39.0; H, 2.0; S, 10.4; Zn 10.6 Found: C, 39.3; H, 1.9; S, 10.3; Zn, 10.6

Copper N-( 8-quinolinyl )trifluoromethanesulfonamide m.p. greater than 300 C.

ANTl-MICROBIAL ACTIVITY The anti-microbial activity of a number of the compounds is exemplified in the following Examples.

The antibacterial activity was determined by a variation of the original agar-plate diffusion method of Vincent and Vincent. The culture media employed are designed to meet the minimum essential requirements for the growth of the various test organisms. They are based on the synthetic glucose-salts medium of Davis and- Mingioli (DG agar). The table below gives the media used for each of the test organisms:

Organism Medium 1. Slupliyluc'or'r'us Ulll'('llS DGY 2. Bari/Ins silblilus DGA 3. Pscudumumls uerugt'uusu DG 4. Escherichia culi DG 5. Srrepmcut'cus Sp. (21 (21 6. Aspergi/lus niger DG 7. Candida ulbicuns DG (21 1 Strains isolated from dental Caries in rats or hamsters at the National Institute of Dental Health and grown in PFY or APT agar.

The culture media used in the foregoing tests were as follows: I

DG: K- HPO 7.0 g PFY: NaCl 6.66 g

NaH PO H O 2.3 g KC] 0.26 g MgSQ .7H- O 0.1 g MgSOOhd 4.7H O 0.14 g (NH SO 1.0 g CaCl .2H O 0.014 g CaC1 .2H- ,O 0.04 g Na HPO .14 g FeSO .7H O 0.01 g KH PO 0.075 g Dextrose 2 g Phenol red 0.001 g lonagar 8.5 g Yeast Extract 0.9 g Dist. Water l 1. Glucose 1.8 g

NaHCO 1.2 g

DGY: DG supplemented with lonagar 8.5 g

1 g per 1. of yeast Dist. Water 1 l. extract DGA: DG supplemented with APT: Trypticase 10.0 g

600 mg/l. glutamic acid 200 rng/l. eystinc 800 mg/l. asparagine 20 mg/l. EDTA disodiunt The agar media were melted in a steam bath, supplements, if any, were added, and the media were cooled to 42 C. in a water bath. Then from 10 to 10 cells or spores of the test organism were added per 10 ml. of agar, and the media were dispensed, at 10 ml. per dish, into 9 cm. circular plastic petri dishes.

The tests were carried out quantitatively by placing 4 ,ul. aliquots of 1%, 0.1% and 0.01% solution of the test chemicals on 6.5 mm. paper discs to give 40, 4.0 and 0.4 ,u g. per disc, respectively.

For the first part of the tests, in serum free media, the same culture media were used as described above. For the second part of the tests, all test organisms were grown in PFY agar supplemented with 10% horse serum. Some of the organisms were grown in desiccators in 10% CO in air (numbers 2, 5 and 6). The others 1, 3, 4 and 7) were grown in air. Plates were incubated at 30 C. for 24 hours (for bacteria and C, albicans) and 48 hours for A. niger. The diameters of the zones of inhibition were measured, and log in was plotted against X where m is the weight of test compound on 9 the disc in ,ug and X is the diameter of the zone of inhi bition in mm.

Leading references to the method used are:

1. Vincent. J. G., and Helen W. Vincent, 1944, Filter-paper disc modification of the Oxford-cup penicillin determination, Proc. Soc. Exptl. Biol. Med. 55;l62 l64.

2. Davis, B. D. and Mingioli, E. S., 1953, Aromatic biosynthesis, Jour. Bact. 66;l29l36.

The data resulting for each compound was placed in a reduced form and the activity presented for comparison as an Activity Index. This scoring method for comparing anti-microbial potency is derived as follows:

Active at l ug.l points Active at llO ug.l0 points Active at'lO-IOO pg-l point Since there are seven test organisms, a maximum of 700 points is possible.

Anti-microbial activity of the compound of Example 4 against Microorganisms 1,2,4,5, gives activity index 10 301. Thus it can be seen that it is a highly active antimicrobial compound. What is claimed is: l. A compound of the formula:

5. A compound according to claim 1 in which n is O. 

1. A COMPOUND OF THE FORMULA:
 2. A compound according to claim 1 in which Rf is CF3.
 3. The compound N-(8-quinolinyl)trifluoromethanesulfonamide according to claim
 2. 4. The compound zinc N-(8-quinolinyl)trifluoromethanesulfonamide according to claim
 2. 5. A compound according to claim 1 in which n is
 0. 